Acetic Acid → HCID 178469012, compound

HRID 525465Notes

Reaction equation

HRID 525465 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]=O)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].CC(O)=O.[CH3:28][C:29]1([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.[BH3-]C#N.[Na+]>C(Cl)Cl>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:32]2[CH2:33][CH2:34][C:29]([CH3:28])([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:30][CH2:31]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 19361805Ethyl 4-methylpiperidine-4-carboxylateHCID 178445787HCID 178445787, compound

Product 1

HCID 178469012HCID 178469012, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-(trans-4-tert-butylcyclohexyloxy)-2-naphthaldehyde (500 mg, 1.6 mmol), AcOH (288 mg, 4.8 mmol, 3.0 eq) and ethyl 4-methylpiperidine-4-carboxylate (410 mg, 2.4 mmol, 1.5 eq) in DCM (5 mL) was stirred at room temperature for 10 min. Then NaBH3CN (300 mg, 4.8 mmol, 3.0 eq) was added. The reaction mixture was stirred at room temperature for 12 h, quenched with water (5 mL) and extracted with DCM (3×10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (Petroleum ether:ethyl acetate=3:1) to give ethyl 1-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)-4-methylpiperidine-4-carboxylate (480 mg, yield: 30%) as a yellow oil. ESI-MS (M+1)+: 466.2. 1HNMR (400 MHz, CDCl3) δ: 7.75˜7.73 (m, 3H), 7.48 (d, 1H), 7.18˜7.15 (m, 2H), 4.28˜4.26 (m, 1H), 4.19˜4.12 (q, 2H), 4.01 (s, 2H), 3.17˜3.15 (m, 2H), 2.59 (br, 2H), 2.29˜2.17 (m, 4H), 1.91˜1.82 (m, 4H), 1.46˜1.43 (m, 3H), 1.30˜1.18 (m, 8H), 0.88 (s, 9H).

Workup

  1. customquenched with water (5 mL)
  2. extractionextracted with DCM (3×10 mL)
  3. washThe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (Petroleum ether:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-40f522e4e5c541dca18e3c89179078a2
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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